In PLoS Genetics this week, a public-private team led by investigators at the University of California, Los Angeles, reports its "comparative analysis of proteome and transcriptome variation in mouse." Using natural genetic variations to perturb transcript and protein levels within inbred strains, the team quantified peptide and transcript levels and found that the "levels of transcripts and proteins correlate significantly for only about half of the genes tested, with an average correlation of 0.27, and the correlations of transcripts and proteins varied depending on the cellular location and biological function of the gene." The team says it was also surprised to find that "transcript levels were more strongly correlated with clinical traits than protein levels."
In another PLoS Genetics paper appearing online this week, a team led by researchers at China's Sichuan Academy of Medical Sciences reports its use of exome sequencing to identify a causative gene for myopia, an autosomal dominant disorder, as well as a "gene potentially responsible for high myopia in a monogenic form." In sequencing the exomes of two individuals affected by high myopia and filtering variants shared between them against the 1,000 Genomes Project and dbSNP131 databases, the team identified a mutation in ZNF644 "as being related to the phenotype of this family," it reports. The team also reports five mutations it observed in 11 different patients, all of which were absent in 600 normal controls. Overall, "our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form," the authors write.
The National Cancer Institute's Rosemary Braun and Kenneth Buetow present a multi-SNP analysis method for genome-wide association studies, which they called Pathways of Distinction Analysis. "The method uses GWAS data and known pathway-gene and gene-SNP associations to identify pathways that permit, ideally, the distinction of cases from controls … [and] is based upon the hypothesis that, if a pathway is related to disease risk, cases will appear more similar to other cases than to controls (or vice versa) for the SNPs associated with that pathway," Braun and Buetow write in PLoS Genetics this week.
Over in PLoS One, the Biomarker Discovery Center Heidelberg's Andreas Keller et al. report novel SNPs for glioblastoma multiforme, which they identified using a combination of specific target selection and next-generation sequencing. "With this approach we identified over 6,000 SNPs, including over 1,300 SNPs located in the targeted genes," Keller et al. write, adding that by "integrating [a] GWAS catalog and known disease-associated SNPs, we found that several of the detected SNPs were previously associated with smoking behavior, body mass index, breast cancer and high-grade glioma."